Dendrodendritic synapses are the major means of horizontal neuronal connectivity within the olfactory bulb. The specific aims of this proposal are to determine the neurochemical mechanisms utilized by these synapses for processing olfactory sensory information. Accomplishment of the specific aims will help clarify the physiological role of dendrodendritic synapses in olfaction and may be relevant to understanding information processing in other sensory systems. GABA is considered an inhibitory neurotransmitter of granule cells at dendrodendritic synapses with neurochemical evidence provided by the laboratory of the investigator. The proposed experiments will detemrine which additional neurotransmitter systems are involved at these synapses by using high-affinity uptake (presynaptic marker) and receptor binding (postsynaptic) techniques. These biochemical neurotransmitter properties will be characterized kinetically and pharmacologically. The neuronal localization of these synaptic processes will be established by electrolytic lesions of the lateral olfactory tract, by intrabulbar kainic acid induced lesions, and by using the murine neurological mutant, Purkinje cell degeneration. The regulatory influences of dendrodendritic neurotransmitters on the presynaptic release, high-affinity uptake and on the postsynaptic receptor binding of GABA will be determined using dendrodendritic synaptosomes (DDS). Preliminary experiments suggest that the mitral cells use glutamate as an excitatory neurotransmitter and have a clonazepam-sensitive benzodiazepine binding site that is functionally associated with the GABA postsynaptic receptor. Initial studies also suggest that GABA efflux from DDS is stimulated by potassium. GABA and glutamate are considered the major inhibitory and excitatory neurotransmitters of the mammalian central nervous system, respectively. Aberrations in these neurotransmitter systems are implicated in such neurological disorders as Huntington's chorea, epilepsy, olivopontocerebellar atrophy, and Parkinson's disease. Since the olfactory bulb is such a rich source of synapses utilizing both GABA and glutamate, it has the potential of serving as a model for these neurotransmitter systems in general.